Nerve growth factor (NGF) is a chemically well-defined polypeptide important to the development and growth of the vertebrate nervous system. For a recent review of the chemistry, biology, and medical implications of NGF please see Mobley et al., New Eng. J. Med. 297: 1096, 1149 & 1211 (1977). Certain neuronal tumors, such as neuroblastoma, will respond in culture to NGF by acquiring a more advanced morphology, by biochemical specialization, and by slowing of growth. Thus, the uncontrolled growth and primitive morphology of neuronal tumors may be subject to manipulation, but a fuller understanding of the molecular processes leading to differentiation will be required. The aim of this project is to define the sequence of events beginning with the interaction of NGF with its receptor and which ultimately culminates in neurite outgrowth and increased activity of neuron-specific enzymes in cultured rat pheochromocytoma cells. It is proposed to study the properties of the NGF receptor, to identify and isolate macromolecular elements crucial for neurite outgrowth, and to identify transcriptional, translational, and post-translational regulatory events. Attempts will be made to identify specific and reversible agonists and inhibitors of differentiation. This supplement proposes to extend such studies to human neuroblastoma cells in culture, particularly as it is not known whether the alterations leading to loss of growth control are the same in rodent as in human cells. Specifically, the aim is to study the effect of NGF on neurite outgrowth and growth rate of eight lines of human neuroblastoma cells, and to correlate the biological effect with studies on binding of NGF to specific binding sites.